Levels of Cytomegalovirus-Reactive Antibody and γδ T Cell Phenotypes Align with Vascular Changes in People Living With HIV.

Abstract

People living with HIV (PLWH) beginning antiretroviral therapy (ART) retain a high burden of cytomegalovirus (CMV). CMV has been implicated in atherosclerosis in healthy adults, and a role in PLWH is plausible. Atherosclerosis has also been linked with γδ T cells and CMV seropositivity with altered γδ T cell profiles in other populations. In our cohort of PLWH starting ART in Jakarta (Indonesia), metrics of the CMV burden correlated with altered profiles of Vδ2^- γδ T cells. Here CMV DNA was sought by RT-PCR as PLWH began ART. γδ T cell subsets were immunophenotyped using flow cytometry, and CMV-reactive antibodies were quantitated by ELISA after fixed intervals on ART. Carotid intima-media thickness (cIMT) was used to assess atherosclerosis. PLWH retained higher levels of CMV-reactive antibody than healthy controls (p = 0.001-0.04), and 50% began ART with detectable CMV DNA. cIMT values rose between 6 and 12 months on ART. At 6 months, cIMT correlated with CMV-reactive antibodies and proportions of activated Vδ2^- γδ T cells (r = 0.56-0.57; p = 0.035-0.042) in PLWH who began ART with detectable CMV DNA. Hence, a high burden of replicating CMV may promote atherosclerosis in PLWH after a period on ART, and the role of activated Vδ2^- γδ T cells warrants further study.